The long term objective of this application is to develop a practical, sensitive and specific approach for the diagnosis of HIV infection in neonates, infants and children. At the present time there is no reliable method for diagnosing HIV infection in early life. HIV serology, which is so useful in adults, is of little value in neonates and infants because of passively transferred maternal antibodies, which may persist up to and sometimes beyond 15 months of age. This proposal is based on the premise that a useful diagnostic approach for this age group can best be developed by evaluating a battery of tests ('multi-test' approach) done concurrently in a large enough sample size which would allow statistically valid comparisons. In our test battery we have included three of what we consider the most promising tests (in-vitro antibody synthesis, serum clonotypic analysis and polymerase chain reaction), as well as tests of restricted value (HIV antigen and antibody) and have coupled these with immunologic analyses. HIV cultures will be done to confirm a positive test or to evaluate an ambiguous result. The rationale behind the multi- test approach is that it would allow us to determine which single test or which particular combination of tests would be most useful for diagnosing HIV infection at specified ages after birth. A cohort of 300 seropositive infants classified as P-O will be enrolled over a 3 year period and each infant will be longitudinally evaluated clinically as well as by the multi-test battery at specified time points for a period of 2 years. The study population will be derived from two inner city hospitals (Brooklyn and Harlem) and from a suburban hospital in Nassau County. Establishing reliable methodology for early diagnosis of HIV infection would fulfill an existing void and facilitate the conduct of clinical trials of anti-HIV therapies in infants and children.